Clinical review and literature analysis of hepatic epithelioid angiomyolipoma in alcoholic cirrhosis: A case report

BACKGROUND Hepatic epithelioid angiomyolipoma(HEA)has a low incidence and both clinical manifestations and imaging lack specificity.Thus,it is easy to misdiagnose HEA as other tumors of the liver,especially in the presence of liver diseases such as hepatitis cirrhosis.This article reviewed the diagnosis and treatment of a patient with HEA and alcoholic cirrhosis,and analyzed the literature,in order to improve the understanding of this disease.CASE SUMMARY A 67-year-old male patient with a history of alcoholic cirrhosis was admitted due to the discovery of a space-occupying lesion in the liver.Based on the patient’s history,laboratory examinations,and imaging examinations,a malignant liver tumor was considered and laparoscopic partial hepatectomy was performed.Postoperative pathology showed HEA.During outpatient follow-up,the patient showed no sign of recurrence.CONCLUSION HEA is difficult to make a definite diagnosis before surgery.HEA has the poten-tial for malignant degeneration.If conditions permit,surgical treatment is recom-mended.

Hepatic venous pressure gradient: Inaccurately estimates portal venous pressure gradient in alcoholic cirrhosis and portal hypertension

BACKGROUND Portal hypertension(PHT)in patients with alcoholic cirrhosis causes a range of clinical symptoms,including gastroesophageal varices and ascites.The hepatic venous pressure gradient(HVPG),which is easier to measure,has replaced the portal venous pressure gradient(PPG)as the gold standard for diagnosing PHT in clinical practice.Therefore,attention should be paid to the correlation between HVPG and PPG.METHODS Between January 2017 and June 2020,134 patients with alcoholic cirrhosis and PHT who met the inclusion criteria underwent various pressure measurements during transjugular intrahepatic portosystemic shunt procedures.Correlations were assessed using Pearson’s correlation coefficient to estimate the correlation coefficient(r)and determination coefficient(R^(2)).Bland-Altman plots were constructed to further analyze the agreement between the measurements.Disagreements were analyzed using paired t tests,and P values<0.05 were considered statistically significant.RESULTS In this study,the correlation coefficient(r)and determination coefficient(R2)between HVPG and PPG were 0.201 and 0.040,respectively(P=0.020).In the 108 patients with no collateral branch,the average wedged hepatic venous pressure was lower than the average portal venous pressure(30.65±8.17 vs.33.25±6.60 mmHg,P=0.002).Hepatic collaterals were identified in 26 cases with balloon occlusion hepatic venography(19.4%),while the average PPG was significantly higher than the average HVPG(25.94±7.42 mmHg vs 9.86±7.44 mmHg;P<0.001).The differences between HVPG and PPG<5 mmHg in the collateral vs no collateral branch groups were three cases(11.54%)and 44 cases(40.74%),respectively.CONCLUSION In most patients,HVPG cannot accurately represent PPG.The formation of hepatic collaterals is a vital reason for the strong underestimation of HVPG.

Spontaneous remission of hepatic myelopathy in a patient with alcoholic cirrhosis:A case report

BACKGROUND Hepatic myelopathy(HM)is a rare neurological complication of advanced cirrhosis.Prognosis of patients with HM is generally poor without timely liver transplantation or interventional therapy.Self-resolving HM in patients with alcoholic cirrhosis has never been reported.CASE SUMMARY A 53-year-old man with alcoholic cirrhosis and recurrent overt hepatic encephalopathy for 1 year was admitted for lower extremity weakness,slow movement,and stumbling gait.The patient was diagnosed with HM after excluding other causes of spastic paraparesis.The patient refused liver transplantation.However,the patient kept total abstinence and received a multidisciplinary treatment for complications of decompensated cirrhosis.The symptoms of HM resolved gradually after 2 years of treatment.All complications of alcoholic cirrhosis resolved after 4 years of follow-up.CONCLUSION The case demonstrates that HM can resolve in patients without liver transplantation after total abstinence and systemic management of complications.

Levels of circulating follicular helper T cells,T helper 1 cells,and the prognostic significance of soluble form of CD40 ligand on survival in patients with alcoholic cirrhosis

Background:Excessive drinkers(ED)and patients with alcoholic liver disease(ALD)are several times more susceptible to bacterial and viral infections and have a decrease in antibody responses to vaccinations.Follicular helper T(TFH)cells are essential to select B cells in the germinal center and to produce antibodies.TFH cells express both a membrane-associated and a soluble form of CD40 ligand(sCD40L),in which the latter form is released to circulation upon T cell activation.The effect of alcohol on TFH cells has not been studied.Objectives:The goals of this study are to determine the levels of TFH and T helper 1(Th1)cells in ED and those with alcoholic cirrhosis(AC)when compared to healthy controls and to determine the prognostic significance of sCD40L in a cohort of patients with AC.Methods:Controls,ED,and those with AC were enrolled.Baseline demographic,laboratory tests,and peripheral blood mononuclear cells(PBMCs)were isolated and assessed via flow cytometry for TFH cells.In vitro study was performed to determine the ability of PBMCs to secrete interferon(IFN)-ɣupon stimulation.Serum sCD40L was also determined and its prognostic significance was tested in a cohort of AC patients.Results:The levels of circulating TFH(cTFH)cells were significantly lower in peripheral blood of subjects with ED and AC compared to controls(P<0.05).IFN-ɣsecretion from PBMCs upon stimulation was also lower in ED and those with cirrhosis.Serum sCD40L was significantly lower in ED and AC when compared to that in controls(P<0.0005).Its level was an independent predictor of mortality.Conclusions:Patients with AC had significantly lower level of cTFH and sCD40L.The level of sCD40L was an independent predictor of mortality in these patients.

Association between alcohol-associated cirrhosis and inpatient complications among COVID-19 patients:A propensity-matched analysis from the United

BACKGROUND Alcohol-associated cirrhosis(AC)contributes to significant liver-related mortality in the United States.It is known to cause immune dysfunction and coagulation abnormalities.Patients with comorbid conditions like AC are at risk of worse clinical outcomes from coronavirus disease 2019(COVID-19).The specific association between AC and COVID-19 mortality remains inconclusive,given the lack of robust clinical evi-dence from prior studies.AIM To study the predictors of mortality and the outcomes of AC in patients hospitalized with COVID-19 in the United States.METHODS We conducted a retrospective cohort study using the National Inpatient Sample(NIS)database 2020.Patients were identified with primary COVID-19 hospitalizations based on an underlying diagnosis of AC.A matched comparison cohort of COVID-19 patients without AC was identified after 1:N propensity score matching based on baseline sociodemographic characteristics and Elixhauser comorbidities.Primary outcomes included median length of stay,median inpatient charges,and in-hospital mortality.Secondary outcomes included a prevalence of systemic complications.RESULTS A total of 1325 COVID-19 patients with AC were matched to 1135 patients without AC.There was no difference in median length of stay and hospital charges in COVID-19 patients with AC compared to non-AC(P>0.05).There was an increased prevalence of septic shock(5.7%vs 4.1%),ventricular fibrillation/ventricular flutter(0.4%vs 0%),atrial fibrillation(13.2%vs 8.8%),atrial flutter(8.7%vs 4.4%),first-degree atrioventricular nodal block(0.8%vs 0%),upper extremity venous thromboembolism(1.5%vs 0%),and variceal bleeding(3.8%vs 0%)in the AC cohort compared to the non-AC cohort(P<0.05).There was no difference in inpatient mortality in COVID-19 patients with non-AC compared to AC,with an odds ratio of 0.97(95%confidence interval:0.78-1.22,P=0.85).Predictors of mortality included advanced age,cardiac arrhythmias,coagulopathy,protein-calorie malnutrition,fluid and electrolyte disorders,septic shock,and upper extremity venous thromboembolism.CONCLUSION AC does not increase mortality in patients hospitalized with COVID-19.There is an increased association between inpatient complications among COVID-19 patients with AC compared to non-AC.

Towards an evaluation of alcoholic liver cirrhosis and nonalcoholic fatty liver disease patients with hematological scales

BACKGROUND Seeking potentially novel blood markers of liver fibrosis and steatosis is constantly of crucial importance.Despite a growing number of studies in this field of hepatology,a certain role of hematological indices in the course of liver disorders has not been fully elucidated,yet.AIM To evaluate a diagnostic accuracy of neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR)and mean platelet volume-to-platelet-ratio(MPR)in the course of alcoholic liver cirrhosis(ALC)and nonalcoholic fatty liver disease(NAFLD).METHODS One hundred forty-two patients with ALC,92 with NAFLD and 68 persons in control group were enrolled in the study.Hematological indices(NLR,PLR and MPR),indirect and direct markers of liver fibrosis(aspartate transaminase to alkaline transaminase ratio,aspartate transaminase to platelet ratio index,fibrosis-4,gamma-glutamyl transpeptidase to platelet ratio,procollagen Ⅰ carboxyterminal propeptide,procollagen Ⅲ aminoterminal propeptide,transforming growth factor-α,platelet-derived growth factor AB,laminin)were measured in each person.Model for end-stage liver disease(MELD)score in ALC group and NAFLD fibrosis score together with BARD score were calculated in NAFLD patients.Receiver operating characteristic(ROC)curves and area under the curve(AUC)values were applied to assess the sensitivity and specificity of examined markers and to evaluate proposed cut-offs of measured indices in the course of ALC and NAFLD.RESULTS MPR and NLR values in ALC patients were significantly higher in comparison to control group;PLR level was significantly lower.MPR and PLR correlated with assessed indirect and direct markers of liver fibrosis.MPR,NLR and PLR correlated with MELD score.NLR level in NAFLD patients was significantly higher in comparison to controls.MPR correlated with indirect markers of liver fibrosis and NAFLD fibrosis score.AUC values and proposed cut-offs for NLR,PLR and MPR in ALC patients were:0.821(>2.227),0.675(<70.445)and 0.929(>0.048),respectively.AUC values and proposed cut-offs for NLR,PLR and MPR in NAFLD group were:0.725(>2.034),0.528(>97.101)and 0.547(>0.038),respectively.CONCLUSION Hematological markers are inseparably connected with serological indices of liver fibrosis in ALC and NAFLD patients.MPR and NLR turned out to be the most powerful parameters in ALC patients.

Trends of alcoholic liver cirrhosis readmissions from 2010 to 2018:Rates and healthcare burden associated with readmissions

BACKGROUND Alcoholic liver cirrhosis(ALC)is a chronic liver disease with varying disease severity.Readmissions of ALC are associated with poor outcomes.AIM To identify and assess trends of readmissions for ALC over an eight-year period.METHODS This retrospective interrupted trend study analysed 30-d readmissions of ALC in the United States from 2010 to 2018 using the National Readmissions Database.Hospitalization for ALC was the reason for index admission obtained using the International Classification of Diseases codes(571.2 and K70.3X).Biodemographic characteristics and hospitalization trends were highlighted over time.A multivariate regression analysis model was used to calculate the trend for riskadjusted odds of 30-d all-cause ALC readmissions,ALC specific readmission rate,ALC readmission proportion,inpatient mortality,mean length of stay(LOS)and mean total hospital cost(THC)following adjustments for age,gender,grouped Charlson Comorbidity Index,insurance,mean household income,and hospital characteristics.RESULTS There was a trend towards increasing total 30-d readmissions of ALC from 7660 in 2010 to 15085 in 2018(P<0.001).Patients readmitted for ALC were noted to have an increasing comorbidity burden over time.We noted a rise in the risk-adjusted 30-d all-cause readmission of ALC from 24.9%in 2010 to 29.9%in 2018(P<0.001).ALC-specific readmission rate increased from 6.3%in 2010 to 8.4%in 2018(P<0.001)while ALC readmission proportion increased from 31.4%in 2010 to 36.3%in 2018(P<0.001).Inpatient mortality for 30-d readmissions of ALC declined from 10.5%in 2010 to 8.2%in 2018(P=0.0079).However,there was a trend towards increasing LOS from 5.6 d in 2010 to 6.3 d in 2018(P<0.001)and increasing THC from 13790 dollars in 2010 to 17150 dollars in 2018(P<0.001).The total days of hospital stay attributable to 30-d readmissions of ALC increased by 119.2%while the total attributable hospital costs increased by 149%by the end of 2018.CONCLUSION There was an increase in the 30-d readmission rate and comorbidity burden for ALC;however,inpatient mortality declined.Additionally,there was a trend towards increasing LOS and THC for these readmissions.

Randomized controlled trial of Qing Gan Huo Xue Prescription in the treatment of alcoholic liver cirrhosis

Objective:To evaluate the efficacy of Qing Gan Huo Xue Prescription(QGHXP)in the treatment of patients with alcoholic liver cirrhosis(ALC)of damp and heat stasis syndrome.Methods:A total of 69 patients with ALC were randomly divided into TCM group(n=35)and control group(n=34).The TCM group was given QGHXP 1 pack TID orally.Control group received polyene phosphatidylcholine capsule 456 mg TID for 24 weeks.The observation measurements are symptom efficacy rate,serum level of liver enzyme,and non-invasive liver cirrhosis evaluation,including liver stiffness measurement(LSM)examininged by FibroTouch,APRI score,FIB-4 index and Maddrey discriminant function.Results:The symptom efficacy rate of the experimental group and the control group was 85.70%and 61.80%(P=0.024).Liver enzyme levels(serum ALP,γ-GT,AST and ALT)of TCM group were lower than those of control group(P<0.05).LSM of TCM group was reduced after treatment,and was significant lower than control group(14.19±1.49)vs.(15.06±1.24)(P<0.05).The APRI scores,FIB-4 index and Maddrey discriminant functions of TCM group were lower than those of control group(P<0.05).Conclusion:QGHXP is an effective alternative for the treatment of damp and heat stasis syndrome of ALC in improving liver function and clinical symptoms.

Hospitalizations for alcoholic liver disease during the COVID-19 pandemic increased more for women,especially young women,compared to men

BACKGROUND Alcoholic liver disease(ALD)remains one of the major indications for liver transplantation in the United States and continues to place a burden on the national healthcare system.There is evidence of increased alcohol consumption during the coronavirus disease 2019(COVID-19)pandemic,and the effect of this on the already burdened health systems remains unknown.AIM To assess the trends for ALD admissions during the COVID-19 pandemic,and compare it to a similar pre-pandemic period.METHODS This retrospective study analyzed all admissions at a tertiary health care system,which includes four regional hospitals.ALD admissions were identified by querying a multi-hospital health system’s electronic database using ICD-10 codes.ALD admissions were compared for two one-year periods;pre-COVID-19 from April 2019 to March 2020,and during-COVID-19 from April 2020 to March 2021.Data were analyzed using a Poisson regression model and admission rates were compared using the annual quarterly average for the two time periods,with stratification by age and gender.Percent increase or decrease in admissions from the Poisson regression model were reported as incident rate ratios.RESULTS One thousand three hundred and seventy-eight admissions for ALD were included.80.7%were Caucasian,and 34.3%were female.An increase in the number of admissions for ALD during the COVID-19 pandemic was detected.Among women,a sharp rise(33%)was noted in those below the age of 50 years,and an increase of 22%in those above 50 years.Among men,an increase of 24%was seen for those below 50 years,and a 24%decrease in those above 50 years.CONCLUSION The COVID-19 pandemic has had widespread implications,and an increase in ALD admissions is just one of them.However,given that women are often prone to rapid progression of ALD,this finding has important preventive health implications.

Leukocyte cell-derived chemotaxin-2 and fibroblast growth factor 21 in alcohol-induced liver cirrhosis

BACKGROUND The importance of early diagnosis of alcoholic liver disease underscores the need to seek better and especially non-invasive diagnostic procedures.Leukocyte cellderived chemotaxin-2(LECT2)has been widely studied to determine its usefulness in monitoring the course of non-alcoholic fatty liver disease but not for alcoholic liver cirrhosis(ALC).AIM To determine the concentration of LECT2 in the blood serum of patients in relation to progressive stages of ALC,its relation to fibroblast growth factor 1(FGF-1)and FGF-21,and to examine the possible wider use of LECT2 in diagnosing ALC.METHODS A retrospective case-control study was conducted with 69 ALC cases and 17 controls with no ALC.Subjects were recruited from the region of Lublin(eastern Poland).Liver cirrhosis was diagnosed based on clinical features,history of heavy alcohol consumption,laboratory tests,and abdominal ultrasonography.The degree of ALC was evaluated according to Pugh-Child criteria(the Pugh-Child score).Blood was drawn and,after centrifugation,serum was collected for analysis.LECT2,FGF-1,and FGF-21 were determined using enzyme-linked immunosorbent assay kits.RESULTS The LECT2 Levels in the control group were 18.99±5.36 ng/mL.In the study groups,they declined with the progression of cirrhosis to 11.06±6.47 ng/mL in one group and to 8.06±5.74 ng/mL in the other(P<0.0001).Multiple comparison tests confirmed the statistically significant differences in LECT2 Levels between the control group and both test groups(P=0.006 and P<0.0001).FGF-21 Levels were 44.27±64.19 pg/mL in the first test group,45.4±51.69 pg/mL in the second(P=0.008),and 13.52±7.51 pg/mL in the control group.The difference between the control group and the second test group was statistically significant(P=0.007).CONCLUSION We suggest that LECT2 may be a non-invasive diagnostic factor for alcoholinduced liver cirrhosis.The usefulness of LECT2 for non-invasive monitoring of alcohol-induced liver cirrhosis was indirectly confirmed by the multiple regression model developed on the basis of our statistical analysis.

Liver Transplantation Outcomes of HBV-,HCV-,and Alcohol-induced Hepatocellular Carcinoma in the United States:Analysis of National Inpatient Samples

Objective Liver transplantation is a current treatment option for hepatocellular carcinoma(HCC).The United States National Inpatient Sample database was utilized to identify risk factors that influence the outcome of liver transplantation,including locoregional recurrence,distant metastasis,and in-hospital mortality,in HCC patients with concurrent hepatitis B infection,hepatitis C infection,or alcoholic cirrhosis.Methods This retrospective cohort study included HCC patients(n=2391)from the National Inpatient Sample database who underwent liver transplantation and were diagnosed with hepatitis B or C virus infection,co-infection with hepatitis B and C,or alcoholic cirrhosis of the liver between 2005 and 2014.Associations between HCC etiology and post-transplant outcomes were examined with multivariate analysis models.Results Liver cirrhosis was due to alcohol in 10.5%of patients,hepatitis B in 6.6%,hepatitis C in 10.8%,and combined hepatitis B and C infection in 24.3%.Distant metastasis was found in 16.7%of patients infected with hepatitis B and 9%of hepatitis C patients.Local recurrence of HCC was significantly more likely to occur in patients with hepatitis B than in those with alcohol-induced disease.Conclusion After liver transplantation,patients with hepatitis B infection have a higher risk of local recurrence and distant metastasis.Postoperative care and patient tracking are essential for liver transplant patients with hepatitis B infection.

Diabetes Mellitus Predicts Occurrence of Cirrhosis and Hepatocellular Cancer in Alcoholic Liver and Non-alcoholic Fatty Liver Diseases

Background and Aims:Alcohol abuse and nonalcoholic fatty liver disease (NAFLD) are common causes of liver disease.Diabetes mellitus (DM) is a common comorbidity among NAFLD patients.We performed this study with the specific aim to examine the impact of DM on progression of alcoholic liver disease (ALD) liver and NAFLD.Methods:Medical charts of 480 patients with ALD or NAFLD (2004-2011) managed at a tertiary center were retrospectively reviewed.NAFLD was diagnosed based on exclusion of other causes of liver disease and alcohol use of <10 g/d.ALD was diagnosed based on alcohol use of >40 g/d in women or >60 g/d in men for >5years.Results:Of 480 patients (307 NAFLD),200 diabetics differed from nondiabetics for:age (52±11 vs.49±11 years;p=0.004);male gender (48% vs.57%;p=0.03);metabolic syndrome (49% vs.30%;p=0.0002);NAFLD (80% vs.56%;p<0.0001);cirrhosis (70% vs.59%;p=0.005);and hepatocellular carcinoma (HCC;8% vs.3%;p=0.009).Over a 3 year median follow-up period,diabetics relative to nondiabetics had a higher probability to develop cirrhosis (60% vs.41%;p=0.022) and HCC (27% vs.10%;p=0.045).There was a trend for increased development of hepatic encephalopathy in diabetics compared to nondiabetics (55% vs.39%;p=0.053),and there was no difference between the two groups in survival or other liver disease complications.Conclusions:DM increased risk for cirrhosis and HCC among patients with ALD and NAFLD.Prospective studies with longer follow-up periods are needed to examine the impact of DM on survival and the role of aggressive HCC screening in diabetic cirrhotics.

Status epilepticus as an initial manifestation of hepatic encephalopathy:A case report

BACKGROUND Status epilepticus in patients with hepatic encephalopathy (HE) is a rare butserious condition that is refractory to antiepileptic drugs, and current treatmentplans are vague. Diagnosis may be difficult without a clear history of cirrhosis.Liver transplantation (LT) is effective to alleviate symptoms, however, there arefew reports about LT in the treatment of status epilepticus with HE. To ourknowledge, this is the first report of status epilepticus present as initialmanifestation of HE.CASE SUMMARY A 59-year-old woman with a 20-year history of heavy drinking was hospitalizedfor generalized tonic-clonic seizures. She reported no history of episodes of HE,stroke, spontaneous bacterial peritonitis, ascites or gastrointestinal bleeding.Neurological examination revealed a comatose patient, without papilledema.Laboratory examination suggested liver cirrhosis. Plasma ammonia levels uponadmission were five times normal. Brain computed tomography (CT) was normal,while abdominal CT and ultrasound revealed mild ascites, liver cirrhosis andsplenomegaly. Electroencephalography (EEG)showed diffuse slow waves rhythm,consistent with HE, and sharp waves during ictal EEG corresponding to clinicalsemiology of focal tonic seizures. The symptoms were reversed by continuousantiepileptic treatment and lactulose. She was given oral levetiracetam, and focalaware seizures occasionally affected her 10 mo after LT.CONCLUSION Status epilepticus could be an initial manifestation of HE. Antiepileptic drugs combined with lactulose are essential for treatment of status epilepticus with HE,and LT is effective to prevent the relapse.

Diagnosis and Management of Alcoholic Liver Disease

Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality.Several factors,including the amount and duration of alcohol consumption,affect the development and progression of alcoholic liver disease (ALD).ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis.Early diagnosis of ALD is important to encourage alcohol abstinence,minimize the progression of liver fibrosis,and manage cirrhosis-related complications including hepatocellular carcinoma.A number of questionnaires and laboratory tests are available to screen for alcohol intake.Liver biopsy remains the gold-standard diagnostic tool for ALD,but noninvasive accurate alternatives,including a number of biochemical tests as well as liver stiffness measurement,are increasingly being utilized in the evaluation of patients with suspected ALD.The management of ALD depends largely on complete abstinence from alcohol.Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure.Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care.Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy.Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit.Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis,with most transplant centers mandating a 6 month period of abstinence from alcohol before listing.Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH.A number of novel targeted therapies for ALD are currently being evaluated in clinical trials.

Alcoholic liver disease: A current molecular and clinical perspective

Heavy alcohol use is the cause of alcoholic liver disease(ALD).The ALD spectrum ranges from alcoholic steatosis to steatohepatitis,fibrosis,and cirrhosis.In Western countries,approximately 50%of cirrhosis-related deaths are due to alcohol use.While alcoholic cirrhosis is no longer considered a completely irreversible condition,no effective anti-fibrotic therapies are currently available.Another significant clinical aspect of ALD is alcoholic hepatitis(AH).AH is an acute inflammatory condition that is often comorbid with cirrhosis,and severe AH has a high mortality rate.Therapeutic options for ALD are limited.The established treatment for AH is corticosteroids,which improve short-term survival but do not affect long-term survival.Liver transplantation is a curative treatment option for alcoholic cirrhosis and AH,but patients must abstain from alcohol use for 6 months to qualify.Additional effective therapies are needed.The molecular mechanisms underlying ALD are complex and have not been fully elucidated.Various molecules,signaling pathways,and crosstalk between multiple hepatic and extrahepatic cells contribute to ALD progression.This review highlights established and emerging concepts in ALD clin-icopathology,their underlying molecular mechanisms,and current and future ALD treatment options.

Hepatocellular carcinoma in alcoholic liver disease: mechanistic considerations and clinical facts

Alcoholic hepatocellular carcinoma(AHCC)represents a lethal stage,emerging in the course of severe injurious stages of alcoholic liver disease including cirrhosis.AHCC only affects a few alcohol consumers,certainly not all individuals who consume large amounts of alcohol over a long period of time,suggesting a role of yet unknown genetic risk or protection factors.Most likely,hepatic DNA is ultimately involved,attacked by intermediate products derived from reactive oxygen species(ROS)generated from cytochrome P4502E1 of the NADPH and oxygen dependent microsomal ethanol-oxidizing system whereby ethanol is metabolized.Ethanol and acetaldehyde are activated to procarcinogens,to be promoted to ultimate carcinogens by ROS and causatives for AHCC instead of any other putative chemical contained in alcoholic beverages.Prevention of HCC associated with cirrhosis is best accomplished by early recognition of alcohol abuse at the stage of alcoholic fatty liver rather than alcoholic hepatitis(AH)or alcoholic steatohepatitis(ASH),leading to the advice of consequent abstinence from alcohol.Abstinence early started effectively prevents AHCC development,as opposed to late begin of abstinence that lacks risk reduction.Although drug therapy may partially be effective in AH or ASH,no established drug options are available for a realistic therapy of AHCC.Liver transplantation is controversially discussed and can be considered,but may be an option for only a few patients on a case by case base.In conclusion,AHCC results from a ROS dependent conversion of ethanol and acetaldehyde to procarcinogens as promoters of AHCC.